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Sökning: id:"swepub:oai:DiVA.org:mau-37152" > The intracellular l...

The intracellular lipid-binding domain of human Na+/H+ exchanger 1 forms a lipid-protein co-structure essential for activity

Hendus-Altenburger, Ruth (författare)
Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark; Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
Vogensen, Jens (författare)
Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
Pedersen, Emilie Skotte (författare)
Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark
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Luchini, Alessandra (författare)
Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen Ø, Denmark
Araya-Secchi, Raul (författare)
Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen Ø, Denmark
Bendsoe, Anne H (författare)
Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark; Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
Prasad, Nanditha Shyam (författare)
Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
Prestel, Andreas (författare)
Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark
Cardenas, Marité (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
Pedraz-Cuesta, Elena (författare)
Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
Arleth, Lise (författare)
Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen Ø, Denmark
Pedersen, Stine F (författare)
Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
Kragelund, Birthe B (författare)
Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark
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 (creator_code:org_t)
2020-12-03
2020
Engelska.
Ingår i: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 3:1
Relaterad länk:
https://doi.org/10.1...
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https://mau.diva-por... (primary) (Raw object)
https://www.nature.c...
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Dynamic interactions of proteins with lipid membranes are essential regulatory events in biology, but remain rudimentarily understood and particularly overlooked in membrane proteins. The ubiquitously expressed membrane protein Na+/H+-exchanger 1 (NHE1) regulates intracellular pH (pHi) with dysregulation linked to e.g. cancer and cardiovascular diseases. NHE1 has a long, regulatory cytosolic domain carrying a membrane-proximal region described as a lipid-interacting domain (LID), yet, the LID structure and underlying molecular mechanisms are unknown. Here we decompose these, combining structural and biophysical methods, molecular dynamics simulations, cellular biotinylation- and immunofluorescence analysis and exchanger activity assays. We find that the NHE1-LID is intrinsically disordered and, in presence of membrane mimetics, forms a helical αα-hairpin co-structure with the membrane, anchoring the regulatory domain vis-a-vis the transport domain. This co-structure is fundamental for NHE1 activity, as its disintegration reduced steady-state pHi and the rate of pHi recovery after acid loading. We propose that regulatory lipid-protein co-structures may play equally important roles in other membrane proteins.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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